16-57628885-AGAGTGT-A

Variant names:

• chr16-57628885-AGAGTGT-A
• rs879267570
• NM_201525.4:c.-36+91_-36+96delAGTGTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_201525.4(ADGRG1):​c.-36+91_-36+96delAGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 122,282 control chromosomes in the GnomAD database, including 400 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (400 hom., cov: 29)
  • Exomes 𝑓: 0.020 (610 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.742
• Publications: 0 publications found

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ADGRG1 Gene-Disease associations (from GenCC):

• bilateral frontoparietal polymicrogyria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000261633 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-57628885-AGAGTGT-A is Benign according to our data. Variant chr16-57628885-AGAGTGT-A is described in ClinVar as Benign. ClinVar VariationId is 1296045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	NM_201525.4	MANE Select	c.-36+91_-36+96delAGTGTG		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+91_-154+96delAGTGTG		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+9012_-154+9017delAGTGTG		intron	N/A	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.-36+84_-36+89delGAGTGT		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8750_-154+8755delGAGTGT		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+58_-154+63delGAGTGT		intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 7292 AN: 122174 Hom.: 397 Cov.: 29

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.00655

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0407

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0299

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0556

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0202 AC: 13252 AN: 657396 Hom.: 610 AF XY: 0.0199 AC XY: 6053 AN XY: 304288

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0831 AC: 983 AN: 11832

American (AMR) AF: 0.0328 AC: 28 AN: 854

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 59 AN: 4172

East Asian (EAS) AF: 0.0791 AC: 252 AN: 3184

South Asian (SAS) AF: 0.0266 AC: 359 AN: 13488

European-Finnish (FIN) AF: 0.0121 AC: 3 AN: 248

Middle Eastern (MID) AF: 0.0208 AC: 27 AN: 1298

European-Non Finnish (NFE) AF: 0.0182 AC: 10958 AN: 600550

Other (OTH) AF: 0.0268 AC: 583 AN: 21770

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0599 AC: 7323 AN: 122282 Hom.: 400 Cov.: 29 AF XY: 0.0608 AC XY: 3662 AN XY: 60264

African (AFR) AF: 0.114 AC: 3915 AN: 34202

American (AMR) AF: 0.0803 AC: 1062 AN: 13232

Ashkenazi Jewish (ASJ) AF: 0.00655 AC: 16 AN: 2444

East Asian (EAS) AF: 0.195 AC: 936 AN: 4806

South Asian (SAS) AF: 0.0405 AC: 147 AN: 3632

European-Finnish (FIN) AF: 0.0254 AC: 228 AN: 8976

Middle Eastern (MID) AF: 0.0275 AC: 6 AN: 218

European-Non Finnish (NFE) AF: 0.0168 AC: 883 AN: 52472

Other (OTH) AF: 0.0606 AC: 103 AN: 1700

Alfa AF: 0.00739 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879267570; hg19: chr16-57662797;